Pharming_Methods

If at all one imagined "pharming," it was under tightly protected, controlled greenhouse conditions. Rather like the pharmaceutical banana that was on display at the National Arboretum in March 2003. It is interesting (horrifying, dismaying) to note (see table below) how the terms of discussion seem to be altering over time.

From the industry: Early on there were assurances that "pharma crops" would be grown only under strictly controlled conditions (what are these conditions?); now there is talk of whether or not to grow the crops in the corn belt (presumably open to all the vagaries of pollen flow and gene flow).

Voices of sanity(?): Notice how, starting from the position of an implicit assumption that controlled conditions means growth in greenhouses, there is, at least in some views, an implicit acceptance of the fact of "test plots." [look here for a view from South Africa]

	Biopharm research/industry spokesperson	Commentary
Dec 2005 April 2005	Pharma-crops grown underground [Nature 434: 1060]	US regulatory body, APHIS, castigated for failing to properly regulate pharmaceutical crop field trials. Audit report (pdf)
Mar 2004 Feb 2004	French pharmaceutical company Meristem Therapeutics receives permit to test a plot of genetically engineered corn at a "secret" site in Phillips County, Colorado. Preventing cross-pollination: Male sterile corn detasseled every 24 hr, planted 28 days after, and 1.5 miles from, other corn, exclusive equipment [Rocky Mountain News March 13, 2004]	"....If drugs must be produced in food crops, then those crops should be grown away from non-drug food crops. ... Simply don't use food plants for producing drugs....Let's grow pharma plants, but let those plants be Arabidopsis, or flax, or duckweed." NBT 22, 133
July 2003 May 2003 Mar 2003	"....federal records show 14 permits for biopharming, or growing drugs with genetically altered plants, in Hawaii were issued between 1999 and 2002. However, the permits do not specify where test plots are, which genes are undergoing alteration, or what kind of substance is being produced....Among concerns we have with these field tests is they use food crops, and they take place in open air." [The Scientist July 30, 2003] "Instead of saying we should or shouldn't grow the pharmaceutical crops in food-producing areas, we're using science to determine which ones are safe to grow in food-producing areas, which ones should be grown in other states, and which ones should not be grown in an open environment at all," said Manjit Misra, lead researcher on the project and director of the Seed Science Center at Iowa State." [The Scientist March 21, 2003] "In addition to requiring a one-mile buffer zone around biopharming fields, USDA will now demand that dedicated equipment and facilities for planting, harvesting and storage be used for the GM crops. The agency will also be overseeing training for personnel to ensure that permit requirements are understood and enforced." [The Scientist March 10, 2003]	"...failure to adequately monitor the test plots of biopharmed corn." NBT 21, 480, May 2003 "A non-ingested plant such as kenaf, used to make paper, might be a more viable alternative" quoting Rissler, UCS. [The Scientist, March 21, 2003] "The US Biotechnology Industry Organization (BIO, Washington, DC) caved in to intense political pressure and revised a previous statement calling for outcrossing biopharmaceutical crops not to be planted in the US corn belt" NBT 21, 3, Jan 2003
Dec 2002 Nov 2002 Aug 2002	"Under pressure from a Corn Belt senator, biotechnology companies have dropped a self-imposed ban on growing pharmaceutical crops in heartland states only a month before the moratorium was scheduled to begin. "We do not wish to appear to encourage discrimination against any part of the country," Biotechnology Industry Organization (BIO) spokeswoman Lisa Dry said." [The Scientist, Dec 11 2002] "Until the science and regulations can assure absolute separation in plants and pharmaceuticals and food for good, we would want the research already garnered to find use for non-food crops instead." Stephanie Child, Grocery Manufactures of America Presumed pharma corn volunteers in soybean fields, ProdiGene fined by USDA ["pharma corn" already was being grown in the open in farmers' fields, with few precautions]	"...a single progenitor plant can produce thousands of seeds after a few months of growth in a greenhouse." NBT 20,777
Apr 2000	"The transgenic maize would be grown under rigorously controlled conditions and only used for the express purpose of vaccine production." NBT 18, 367
Mar 2000
Since 1992	Look here for history of release permits

Some of the problems identified by the USDA-APHIS audit:

The exact locations of GE field test sites are not known. There is no follow-up. In January 2005 APHIS requested voluntary submission of GPS coordinates/other details to identify test fields.
Details of containment are not required from applicants. If a field site is selected for inspection, the notification holder is allowed to provide a verbal description of the same.
Permit holders are not required to report on how the 'pharma-crop' is disposed of. The auditors found large harvests that were in storage for over a year without permission.
The field inspections are not done 5 times during the growing season, as stated by APHIS.

Plant-to-pill pharming takes transgenics underground: Nature 2005.

Fears of gene transfer have dogged attempts to create transgenic crops that produce pharmaceuticals. No one wants livestock vaccines turning up in breakfast cereal, for example. But underground agriculture could provide one solution, according to the latest results from an experiment in which corn, or maize, was grown in a disused quarry.

The first crops have been illuminated for about a year by artificial light and are doing well, says Cary Mitchell, a horticulturalist at Purdue University in West Lafayette, Indiana. Mitchell's team presented results on the crop at a US Department of Agriculture (USDA) meeting held last month in Tucson, Arizona.

No drug-producing crops have been tried yet, but the team hopes eventually to see the plants turned into pills in a seamless underground process. The idea could work, says Norman Ellstrand, a gene-flow expert at the University of California, Riverside. "But if they don't field-release it, they don't have to report it to the USDA, which is a little worrying," he add

Drugs in crops--the unpalatable truth
Editorial, Nature Biotechnology, v22, p133, February 2004

"Many companies, among them Diversa, Dow, Epicyte, Samyang Genex, Meristem Therapeutics, Maxygen and ProdiGene are exploring the expression of biopharmaceuticals in corn (maize)—130 acres of which were grown in the United States in 2002 (of a total transgenic acreage of 31.1 million). Other organizations are looking at other major crops: rice, potatoes, alfalfa. One might expect—and some in the industry obviously do—that drug production in plants could be good for the image of GM crops. After all, new/cheaper medicines are the sort of thing that consumers want.

The problem is—as anti-GM lobbyists have argued already—that the production of drugs or drug intermediates in food or feed crop species bears the potential danger that pharmaceutical substances could find their way into the food chain through grain admixture, or pollen-borne gene flow (in maize, at least) or some other accidental mix-up because of the excusably human inability to distinguish between crops for food and crops for drugs. The 'contamination' of soybeans and non-GM corn in 2002 with a corn engineered by Prodigene to produce an experimental pig vaccine shows just how plausible this is (Nat. Biotechnol. 21, 3, 2003). This position is not anti-GM (something industry should appreciate)—we should be concerned about the presence of a potentially toxic substance in food plants. After all, is this really so different from a conventional pharmaceutical or biopharmaceutical manufacturer packaging its pills in candy wrappers or flour bags or storing its compounds or production batches untended outside the perimeter fence?"

Will we reap what biopharming sows?
By Henry I. Miller, Nature Biotechnology, v21, p480, May 2003

Puzzling industry response to ProdiGene fiasco
By Jeffrey L. Fox, Nature Biotechnology, v21, p3, Jan 2003

"In December, officials from the US Department of Agriculture (USDA; Washington, DC), working with the Food and Drug Administration (FDA; Rockville, MD), imposed a $250,000 fine against ProdiGene (College Park, TX) for violations of the Plant Protection Act. Meanwhile, the US Biotechnology Industry Organization (Washington, DC) caved in to intense political pressure and revised a previous statement calling for outcrossing biopharmaceutical crops not to be planted in the US corn belt. These awkward developments come at a delicate moment for companies working to develop plants that produce pharmaceutical or industrial products."

Uncorking the biomanufacturing bottleneck
By Alan Dove, Nature Biotechnology, v20, p777, August 2002

Edible Vaccine success
By Keely Savoie, Nature Biotechnology, V18 p 367, April 2000

"ProdiGene (College Station, TX) announced in February that its patented edible vaccine confers protection against the common transmissible gastrointestinal virus in pigs. The vaccine, produced from maize genetically modified to express antigens of the virus, is the first of its kind to demonstrate efficacy against a viral pathogen in animal trials and is expected to be commercially available for pigs in two to three years after going through the same US Department of Agriculture approval processes as traditional vaccines. ....'The transgenic maize would be grown under rigorously controlled conditions and only used for the express purpose of vaccine production."

Applicant	Release Permit issued	States	Num Permits	Registered 'article'
Noble Foundation	1992	OK	1	Alfalfa
R J Reynolds	1995	NC	1	TMV
Limagrain	1998	IA,IL,IA	4	Corn
Agracetus	1999	IA,IN,WI	1	Corn
Biosource	1991-1999	KY,NC,FL	7	TMV, TEV
Pioneer	1996-2000	CA,NE	2	Rapeseed, Corn
Applied Phytologics	1996-2000	CA,HI	6	Rice
Large Scale Biology	1997-2004	KY, FL	3	TMV**, Tobacco
Prodigene	1997-2004	TX,PR,IA,FL,HI, NE,IA,KS	22	Tomato, Corn
Monsanto	1998-2001	FL,TX,FL,PR,HI, CA,MO,WA,WI	9	Corn
CropTech	1999-2002	VA,SC	7	Tobacco
Washington State Univ	2000-4	WA	2	Barley
Horan Bros	2001	IA	1	Corn
Hawaii Agricultural Res	2001	HI	1	Sugarcane
Dow	2001-2	AZ,CA,HI	2	Corn
Iowa State University	2001-4	IA	1	Corn
Meristem Therapeutics	2002-3	CO,KY,VA	3	Corn
Garst	2003	HI	1	Corn
Emlay	2003	ND.NV	1	Safflower***
Chlorogen	2003	SC	1	Tobacco
Planet Biotechnology	2004	KY	1	Tobacco